Cancer and mortality risks of patients with scoliosis from radiation exposure: a systematic review and meta-analysis.

PURPOSE: The study aimed for unraveling the long-term health impact of cumulative radiation exposure from full-spine radiographs on children/adolescents with scoliosis. METHODS: All cohort, case-control or cross-sectional studies about radiation exposure to scoliosis patients with follow-up period as 20 years or more were included. Meta-analyses were performed for outcomes reported in two or more studies. RESULTS: A total of 9 eligible studies involving 35,641 participants between 1912 and 1990 fulfilled the inclusion criteria, including 18,873 patients with scoliosis and 16,768 controls as regional matched general population. The average number of full-spine radiographs was 23.13 (range: 0-618) according to 14,512 patients between 1912 and 1990 in five studies. The estimated mean cumulated radiation dose of breast was 11.35 cGy. In comparison with controls, pooled incidence rates of cancer, breast cancer and cancer mortality of patients with scoliosis were statistically significant higher [rate of cancer, odds risk (OR) = 1.46, p < 0.00001; breast cancer, OR = 1.20, p = 0.02; cancer mortality, OR = 1.50, p < 0.00001]. No statistically significant differences were found in terms of reproductive events for scoliosis patients, pulmonary function and physical activity for adolescent idiopathic scoliosis patients. CONCLUSIONS: Based on 35,641 participants with over 20 years' observations from 1912 to 1990, repeated radiographs and pertaining cumulative radiation dose resulted in elevated rates of cancer, breast cancer and cancer mortality for children/adolescents with scoliosis in comparison with matched general population. It is recommended that low-radiation or radiation-free and efficient methods should be used to monitor the evolution of children/adolescents with scoliosis.

Landscape of RNAs in human lumbar disc degeneration.

Accumulating evidence indicates noncoding RNAs (ncRNAs) fine-tune gene expression with mysterious machinery. We conducted a combination of mRNA, miRNA, circRNA, LncRNA microarray analyses on 10 adults' lumbar discs. Moreover, we performed additional global exploration on RNA interacting machinery in terms of in silico computational pipeline. Here we show the landscape of RNAs in human lumbar discs. In general, the RNA-abundant landscape comprises 14,635 mRNAs (37.93%), 2,059 miRNAs (5.34%), 18,995 LncRNAs (49.23%) and 2,894 (7.5%) circRNAs. Chromosome 1 contributes for RNA transcription at most (10%). Bi-directional transcription contributes evenly for RNA biogenesis, in terms of 5' to 3' and 3' to 5'. Despite the majority of circRNAs are exonic, antisense (1.49%), intergenic (0.035%), intragenic (1.69%), and intronic (6.29%) circRNAs should not be ignored. A single miRNA could interact with a multitude of circRNAs. Notably, CDR1as or ciRS-7 harbors 66 consecutive binding sites for miR-7-5p (previous miR-7), evidencing our pipeline. The majority of binding sites are perfect-matched (78.95%). Collectively, global landscape of RNAs sheds novel insights on RNA interacting mechanisms in human intervertebral disc degeneration.

Noncoding RNAs in human intervertebral disc degeneration: An integrated microarray study.

Accumulating evidence indicates that noncoding RNAs play important roles in a multitude of biological processes. The striking findings of miRNAs (microRNAs) and lncRNAs (long noncoding RNAs) as members of noncoding RNAs open up an exciting era in the studies of gene regulation. More recently, the reports of circRNAs (circular RNAs) add fuel to the noncoding RNAs research. Human intervertebral disc degeneration (IDD) is a main cause of low back pain as a disabling spinal disease. We have addressed the expression profiles if miRNAs, lncRNAs and mRNAs in IDD (Wang et al., J Pathology, 2011 and Wan et al., Arthritis Res Ther, 2014). Furthermore, we thoroughly analysed noncoding RNAs, including miRNAs, lncRNAs and circRNAs in IDD using the very same samples. Here we delineate in detail the contents of the aforementioned microarray analyses. Microarray and sample annotation data were deposited in GEO under accession number GSE67567 as SuperSeries. The integrated analyses of these noncoding RNAs will shed a novel light on coding-noncoding regulatory machinery.

Cervical open-door laminoplasty technique with simple sutures and bone grafts: a single institutional study with 30 consecutive cases.

BACKGROUND: Expansive open-door laminoplasty is widely accepted as a reliable procedure for cervical myelopathy. However, one acknowledged complication is spring-back complication or closure of the door which may result in restenosis of cervical canal and neurologic deterioration. The study aimed for addressing our cervical open-door laminoplasty technique with sutures and bone grafts and subsequently the follow-up outcomes. METHODS: Thirty consecutive patients who underwent open-door laminoplasty with the novel technique were included and followed for minimum 5 years from Jan 2006 to Dec 2007. Anteroposterior diameter (APD) of the vertebral canal of C4 was measured in lateral cervical radiographs. Neurologic scenarios were noted using the Japanese Orthopaedic Association (JOA) scores. RESULTS: Twenty-five males (83.3%) and five (16.7%) females with an average follow-up of 68 months were enrolled. The preoperative APD was 13.22 mm (±1.15), whereas the postoperative APD increased to 31.23 mm (±2.43) with an expansion ratio of 136.23% (P < 0.05). The JOA score increased from 8.5 preoperatively to 13.45 postoperatively with a recovery rate of 58.2% (P < 0.05). The elevated laminas were maintained open during the follow-up period. CONCLUSIONS: Our technique with sutures and bone graft for laminoplasty is a simple and efficient method for maintaining the decompression of cervical canal and neurologic improvement.

Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery.

As a main contributing factor to low back pain, intervertebral disc degeneration (IDD) is the fundamental basis for various debilitating spinal diseases. The pros and cons of current treatment modalities necessitate biological treatment strategies targeting for reversing or altering the degeneration process in terms of molecules or genes. The advances in stem cell research facilitate the studies aiming for possible clinical application of stem cell therapies for IDD. Human NP cells are versatile with cell morphology full of variety, capable of synthesizing extracellular matrix components, engulfing substances by autophagy and phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas and FasL as significant omens of immune privileged sites. Human discs belong to immune privilege organs with functional FasL expression, which can interact with invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by decreased expression level of FasL with dysfunctional FasL, which in turn unbalances the interaction between NP cells and immune cells. Certain modulation factors might play a role in the process, such as miR-155. Accumulating evidence indicates that Fas-FasL network expresses in a variety of stem cells. Given the expression of functional FasL and insensitive Fas in stem cells (we term as FasL privilege), transplantation of stem cells into the disc may regenerate the degenerative disc by not only differentiating into NP-like cells, increasing extracellular matrix, but also reinforce immune privilege via interaction with immune cells by Fas-FasL network.

Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study.

INTRODUCTION: In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD. METHODS: An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation. RESULTS: Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes. CONCLUSIONS: This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD.